The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

• Published in: Cells (Basel, Switzerland) Switzerland), 2019-10, Vol.8 (10), p.1280
• Main Authors: Maglione, Alessandro, Rolla, Simona, Mercanti, Stefania Federica De, Cutrupi, Santina, Clerico, Marinella
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; adaptive immune system; Adaptive Immunity - genetics; Adaptive Immunity - physiology; Animals; Anti-inflammatory agents; Central nervous system; Cytokines; Demyelination; Disease; DNA methylation; Epigenetics; epigenome; Epigenome - genetics; Epigenome - physiology; Estradiol - metabolism; Estrogen receptors; Estrogens; Estrogens - metabolism; Female; Fetuses; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Gene regulation; Hormones; Humans; Immune system; Immunological tolerance; Immunology; Inflammatory diseases; Ligands; Lymphocytes; Menopause; Molecular modelling; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Neurodegeneration; Neuroprotection; Pathogenesis; Pregnancy; Proteins; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Recruitment; Review; Transcription; Transcription factors; Womens health
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8101280

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS.